Current Treatment Options in Neurology

, Volume 15, Issue 3, pp 241–258 | Cite as

Management of Secondary Progressive Multiple Sclerosis: Prophylactic Treatment—Past, Present, and Future Aspects

  • Paulus S. RommerEmail author
  • Olaf Stüve

Opinion statement

Whereas the number of treatment options in relapsing-remitting multiple sclerosis (RRMS) is growing constantly, alternatives are rare in the case of secondary-progressive multiple sclerosis (SPMS). Besides mitoxantrone in North America and Europe, interferon beta-1b and beta-1a are approved for treatment in Europe. Glucocorticosteroids, azathioprine, intravenous immunoglobulins (IVIG) and cyclophosphamide (CYC), although not approved, are commonly utilized in SPMS. Currently monoclonal antibodies (mab), and masitinib are under examination for treatment for SPMS. Hematopoietic stem cell transplantation and immunoablative stem cell transplantation are therapies with the aim of reconstitution of the immune system. This review gives information on the different therapeutics and the trials that tested them. Pathophysiological considerations are presented in view of efficacy of the therapeutics. In addition, therapeutics that showed no efficacy in trials or with unacceptable side effects are topics of this review.


Secondary progressive multiple sclerosis Interferon beta-1b Interferon beta-1a Mitoxantrone Glucocorticosteroids Azathioprine Intravenous immunoglobulins Cyclophosphamide Masitinib Daclizumab Rituximab Linomide Treatment Prophylactic treatment Management 


Conflict of Interest

Paulus S. Rommer has served as a consultant for Bayer.

Olaf Stüve has received grant support from Teva Pharmaceuticals; served as a consultant for Biogen Idec, Genzyme, Novartis, and Sanofi Aventis; had travel/accommodations expenses covered/reimbursed by Teva Pharmaceuticals; served on boards for Archives of Neurology and Therapeutic Advances in Neurological Disorders; and received fees for participation in review activities such as data monitoring boards, statistical analysis, and end point committees from Teva Pharmaceuticals.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Lublin FD, Reingold SC. Sclerosis. Neurology. 1996;46(4):907–11.PubMedCrossRefGoogle Scholar
  2. 2.
    Weinshenker BG. The natural history of multiple sclerosis: update 1998. Semin Neurol. 1998;18(3):301–7.PubMedCrossRefGoogle Scholar
  3. 3.••
    Frischer JM, Bramow S, Dal-Bianco A, Lucchinetti CF, Rauschka H, Schmidbauer M, et al. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain. 2009;132:1175–89. Important publication that provides fundamental insights in the pathophysiology of multiple sclerosis.PubMedCrossRefGoogle Scholar
  4. 4.
    Luessi F, Siffrin V, Zipp F. Neurodegeneration in multiple sclerosis: novel treatemnt strategies. Expert Rev Neurother. 2012;12(9):1061–77.PubMedCrossRefGoogle Scholar
  5. 5.
    Lassmann H. Cortrical lesions in multiple sclerosis: inflammation vs neurodegeneration. Brain. 2012;135(Pt 10):2904–5.PubMedCrossRefGoogle Scholar
  6. 6.••
    Lassmann H, van Horssen J, Mahad D. Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol. 2012. doi: 10.1038/nrneurol.2012.168. Fundamental concepts pertaining to the pathophysiology of multiple sclerosis are presented in this review.PubMedGoogle Scholar
  7. 7.••
    Kieseier BC, Stüve O. A critical appraisal of treatment decisions in multiple sclerosis--old vs new. Nat Rev Neurol. 2011;7(5):255–62. In this review, the anticipated benefits of novel therapies, including reduction in disease activity, possible prevention of disability, and improvement in quality of life, are outlined. In addition, the current acceptance of potential risks — including serious or even life-threatening adverse effects, the likelihood of which may rise with increased cumulative exposure to a particular agent — by patients with MS are reviewed.PubMedCrossRefGoogle Scholar
  8. 8.
    Shirani A, Zhao Y, Karim ME, Evans C, Kingwell E, van der Kop ML, et al. Association between use of interferon beta and progression of disability in patients with relapsing-remitting multiple sclerosis. JAMA. 2012;308(3):247–56.PubMedCrossRefGoogle Scholar
  9. 9.
    Greenberg BM, Balcer L, Calabresi PA, Cree B, Cross A, Frohman T, et al. interferon beta use and disability prevention in relapsing-remitting Multiple Sclerosis. Arch Neurol. 2012;1–4: doi: 10.1001/jamaneurol.2013.1017.
  10. 10.
    Derfuss T, Kappos L. Evaluating the potential benefit of interferon treatment in Multiple Sclerosis. JAMA. 2012;308(3):290–1.PubMedCrossRefGoogle Scholar
  11. 11.
    Kobelt G, Berg J, Lindgren P, et al. Costs and quality of life of patients with Multiple Sclerosis in Europe. J Neurol Neurosurg Psychiatry. 2006;77:918–26.PubMedCrossRefGoogle Scholar
  12. 12.
    European Study Group on Interferon beta-1b in secondary progressive MS. Placebo-controlled multicenter randomized trial of interferon ß-1b in treatment of secondary progressive Multiple Sclerosis. Lancet. 1998;352(9139):1491–7.CrossRefGoogle Scholar
  13. 13.
    Panitch H, Miller A, Paty D, Weinshenker B, North American Study Group on Interferon beta-1b in secondary progressive MS. Interferon beta-1b in secondary progressive MS: results from a 3-year controlled study. Neurology. 2004;63(10):1788–95.PubMedCrossRefGoogle Scholar
  14. 14.••
    Kappos L, Weinshenker B, Pozzilli C, Thompson AJ, Dahlke F, Beckmann K, et al. Interferon beta-1b in secondary progressive MS: a combined analysis of the two trials. Neurology. 2004;63(10):1779–87. A important comparison of the two trials is presented. Differences between the trials are highlighted.PubMedCrossRefGoogle Scholar
  15. 15.
    Cohen JA, Cutter GR, Fischer JS, Goodman AD, Heidenreich FR, Kooijmans MF, et al. Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology. 2002;59(5):679–87.PubMedCrossRefGoogle Scholar
  16. 16.
    Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-Beta-1a in MS (SPECTRIMS) Study Group. Randomized controlled trial of interferon- beta-1a in secondary progressive MS: clinical results. Neurology. 2001;56(11):1496–504.CrossRefGoogle Scholar
  17. 17.
    Watson CM, Davison AN, Baker D, O’Neill JK, Turk JL. Suppression of demyelination by mitoxantrone. Int J Immunopharmacol. 1991;13(7):923–30.PubMedCrossRefGoogle Scholar
  18. 18.
    Noseworthy JH, Hopkins MB, Vandervoort MK, Karlik SJ, Lee DH, Penman M, et al. An open-trial evaluation of mitoxantrone in the treatment of progressive MS. Neurology. 1993;43(7):1401–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Hartung HP, Gonsette R, König N, Kwiecinski H, Guseo A, Morrissey SP, et al. Mitoxantrone in Multiple Sclerosis Study Group (MIMS). Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomized, multicenter trial. Lancet. 2002;360(9350):2018–25. Important trial.Google Scholar
  20. 20.
    De Castro S, Cartoni D, Millefiorini E, Funaro S, Gasperini C, Morino S, et al. Noninvasive assessment of mitoxantronecardiotoxicity in relapsing remitting Multiple Sclerosis. J Clin Pharmacol. 1995;35(6):627–32.PubMedCrossRefGoogle Scholar
  21. 21.
    Yudkin PL, Ellison GW, Ghezzi A, Goodkin DE, Hughes RA, McPherson K, et al. Overview of azathioprine treatment in Multiple Sclerosis. Lancet. 1991;338(8774):1051–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Milanese C, La Mantia L, Salmaggi A, Eoli MA. Double blind study on azathioprine efficacy in Multiple Sclerosis: final report. J Neurol. 1993;240(5):295–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Steck AJ, Regli F, Ochsner F, Gauthier G. Cyclosporine vs azathioprine in the treatment of Multiple Sclerosis: 12-month clinical and immunological evaluation. Eur Neurol. 1990;30(4):224–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Bryant J, Clegg A, Milne R. Systematic review of immunomodulatory drugs for the treatment of people with Multiple Sclerosis: is there good quality evidence on effectiveness and cost? J Neurol Neurosurg Psychiatry. 2001;70(5):574–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Fernández O, Guerrero M, Mayorga C, Muñoz L, Leán A, Luque G, et al. Combination therapy with interferon ß-1b and azathioprine in secondary progressive Multiple Sclerosis. A two-year pilot study. J Neurol. 2002;249(8):1058–62.PubMedCrossRefGoogle Scholar
  26. 26.
    Evans WE. Pharmacogenetics of thiopurine S-methyltransferase and thiopurine therapy. Ther Drug Monit. 2004;26(2):186–91.PubMedCrossRefGoogle Scholar
  27. 27.
    Weiner HL, Cohen JA. Treatment of Multiple Sclerosis with cyclophosphamide: critical review of clinical and immunological effects. Mult Scler. 2002;8:142–54.PubMedCrossRefGoogle Scholar
  28. 28.
    Bahr U, Schulten HR, Hommes OR, Aerts F. Determination of cyclophosphamide in urine, serum, and cerebrospinal fluid of Multiple Sclerosis patients by field desorption mass spectrometry. Clin Chim Acta. 1980;103(2):183–92.PubMedCrossRefGoogle Scholar
  29. 29.
    Elkhalifa A, Weiner H. Cyclophosphamide treatment of MS: current therapeutic approaches and treatment regimens. Int MS. 2010;17(1):12–8.Google Scholar
  30. 30.
    Hauser SL, Dawson DM, Lehrich JR, Beal MF, Kevy SV, Propper RD, et al. Intensive immunosuppression in progressive Multiple Sclerosis. A randomized, three-arm study of high-dose intravenous cyclophosphamide, plasma exchange, and ACTH. N Engl J Med. 1983;308:173.PubMedCrossRefGoogle Scholar
  31. 31.
    The Canadian Cooperative Multiple Sclerosis Study Group. The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive Multiple Sclerosis. Lancet. 1991;337:441.Google Scholar
  32. 32.
    Zephir H, de Seze J, Duhamel A, Debouverie M, Hautecoeur P, Lebrun C, et al. Treatment of progressive forms of Multiple Sclerosis by cyclophosphamide: a cohort study of 490 patients. J Neurol Sci. 2004;218(1–2):73–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Awad A, Stüve O. Cyclophosphamide in Multiple Sclerosis: scientific rationale, history and novel treatment paradigms. Ther Adv Neurol Disord. 2009;2(6):50–61.PubMedCrossRefGoogle Scholar
  34. 34.
    Goodkin DE, Kinkel RP, Weinstock-Guttman B, VanderBrug-Medendrop S, Secic M, Gogol D, et al. A phase II study of i.v. methylprednisolone in secondary-progressive Multiple Sclerosis. Neurology. 1998;51:239.PubMedCrossRefGoogle Scholar
  35. 35.
    Frequin ST, Lamers KJ, Barkhof F, Borms GF, Hommes OR. Follow-up study of MS patients treated with high-dose intravenous methylprednisolone. Acta Neurol Scand. 1994;90(2):105–10.PubMedCrossRefGoogle Scholar
  36. 36.
    Bergamaschi R, Versino M, Raiola E, Citterio A, Cosi V. High-dose methylprednisolone infusion in relapsing and in chronic progressive Multiple Sclerosis patients. One year follow-up. Acta Neurol. 1993;15(1):33–43.Google Scholar
  37. 37.
    Hohol MJ, Olek MJ, Orav EJ, Stazzone L, Hafler DA, Khoury SJ, et al. Treatment of progressive Multiple Sclerosis with pulsed cyclophosphamide/methylprednisolone: response to therapy is linked to the duration of progressive disease. Mult Scler. 1999;6(5):403–9.Google Scholar
  38. 38.
    Winkelmann A, Zettl UK. Use of intravenous immunoglobulin in the treatment of immune-mediated demyelinating diseases of the nervous system. Curr Pharm Des. 2012;18(29):4570–82.PubMedCrossRefGoogle Scholar
  39. 39.
    Hommes OR, Sørensen PS, Fazekas F, Enriquez MM, Koelmel HW, Fernandez O, et al. Intravenous immunoglobulin in secondary progressive Multiple Sclerosis: randomized placebo-controlled trial. Lancet. 2004;364(9440):1149–56.PubMedCrossRefGoogle Scholar
  40. 40.
    Fazekas F, Sørensen PS, Filippi M, Ropele S, Lin X, Koelmel HW, et al. ESIMS. MRI results from the European Study on Intravenous Immunoglobulin in Secondary Progressive Multiple Sclerosis (ESIMS). Mult Scler. 2005;11(4):433–40.PubMedCrossRefGoogle Scholar
  41. 41.
    Pöhlau D, Przuntek H, Sailer M, Bethke F, Koehler J, König N, et al. Intravenous immunoglobulin in primary and secondary chronic progressive Multiple Sclerosis: a randomized placebo controlled multicenter study. Mult Scler. 2007;13:1107–17.PubMedCrossRefGoogle Scholar
  42. 42.
    Frohman EM, Brannon K, Racke MK, Hawker K. Mycophenolat mofetil in Multiple Sclerosis. Clin Neuropharmacol. 2004;27(2):80–3.PubMedCrossRefGoogle Scholar
  43. 43.
    Simoni Y, Diana J, Ghazarian L, Beaudoin L, Lehuen A. Therapeutic manipulation of natural killer (NK). T cells in autoimmunity: are we close to reality? Clin Exp Immunol. 2013;171(1):8–19.PubMedCrossRefGoogle Scholar
  44. 44.
    Bielekova B, Richert N, Howard T, Blevins G, Markovic-Plese S, McCartin J, et al. Humanized anti-CD25 (daclizumab) inhibits disease activity in Multiple Sclerosis patients failing to respond to interferon beta. Proc Natl Acad Sci U S A. 2004;101(23):8705–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Rose JW, Watt HE, White AT, Carlson NG. Treatment of Multiple Sclerosis with an anti-interleukin-2 receptor monoclonal antibody. Ann Neurol. 2004;56:864–7.PubMedCrossRefGoogle Scholar
  46. 46.
    Rose JW, Burns JB, Bjorklund J, Klein J, Watt HE, Carlson NG. Daclizumab phase II trial in relapsing and remitting Multiple Sclerosis: MRI and clinical results. Neurology. 2007;69:785–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Al-Izki S, Pryce G, Jackson SJ, Giovannoni G, Baker D. Immunosuppression with FTY720 is insufficient to prevent secondary progressive neurodegeneration in experimental autoimmune encephalomyelitis. Mult Scler. 2011;17(8):939–48.PubMedCrossRefGoogle Scholar
  48. 48.
    Bonab MM, Sahraian MA, Aghsaie A, Karvigh SA, Hosseinian SM, Nikbin B, et al. Autologous mesenchymal stem cell therapy in progressive Multiple Sclerosis: an open label study. Curr Stem Cell Res Ther. 2012. [Epub ahead of print].Google Scholar
  49. 49.
    Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, et al. Autologous mesenchymal stem cells for the treatment of secondary progressive Multiple Sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol. 2012;11(2):150–6. doi: 10.1016/S1474-4422(11)70305-2 [Epub Jan 10, 2012].PubMedCrossRefGoogle Scholar
  50. 50.
    Reston JT, Uhl S, Treadwell JR, Nash RA, Schoelles K. Autologous hematopoietic cell transplantation for Multiple Sclerosis: a systematic review. Mult Scler. 2011;17(2):204–13 [Epub Oct 4, 2010].PubMedCrossRefGoogle Scholar
  51. 51.
    Vermersch P, Benrabah R, Schmidt N, Zéphir H, Clavelou P, Vongsouthi C, et al. Masitinib treatment in patients with progressive Multiple Sclerosis: a randomized pilot study. BMC Neurol. 2012;12:36. doi: 10.11866/1471-2377-12-36.PubMedCrossRefGoogle Scholar
  52. 52.
    Tubridy N, Behan PO, Capildeo R, Chaudhuri A, Forbes R, Hawkins CP, et al. The effect of anti-alpha4 integrin antibody on brain lesion activity in MS. The UK Antegren Study Group. Neurology. 1999;53(3):466–72.PubMedCrossRefGoogle Scholar
  53. 53.
    Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, et al. A randomized, placebo-controlled trial of natalizumab for relapsing Multiple Sclerosis. N Engl J Med. 2006;354(9):899–910.Google Scholar
  54. 54.
    O'Connor PW, Goodman A, Willmer-Hulme AJ, Libonati MA, Metz L, Murray RS, et al. Randomized multicenter trial of natalizumab in acute MS relapses: clinical, and MRI effects. Neurology. 2004;62(11):2038–43.Google Scholar
  55. 55.
    Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, et al. B-cell depletion with rituximab in relapsing-remitting Multiple Sclerosis. N Engl J Med. 2008;358(7):676–88.Google Scholar
  56. 56.
    Bar-Or A, Calabresi PA, Arnold D, Markowitz C, Shafer S, Kasper LH, et al. Rituximab in relapsing-remitting Multiple Sclerosis: a 72-week, open-label, phase I trial. Ann Neurol. 2008;63(3):395–400.PubMedCrossRefGoogle Scholar
  57. 57.
    Rommer PS, Patejdl R, Winkelmann A, Benecke R, Zettl UK. Rituximab for secondary progressive Multiple Sclerosis: a case series. CNS Drugs. 2011;25(7):607–13.PubMedCrossRefGoogle Scholar
  58. 58.
    Hawker K, O'Connor P, Freedman MS, Calabresi PA, Antel J, Simon J, et al. Rituximab in patients with primary progressive Multiple Sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol. 2009;66(4):460–71.Google Scholar
  59. 59.
    Coles AJ, Wing MG, Molyneux P, Paolillo A, Davie CM, Hale G, et al. Monoclonal antibody treatment exposes three mechanisms underlying the clinical course in Multiple Sclerosis. Ann Neurol. 1999;46(3):296–304.PubMedCrossRefGoogle Scholar
  60. 60.
    Paolillo A, Coles AJ, Molyneux PD, Gawne-Cain M, MacManus D, Barker GJ, et al. Quantitative MRI in patients with secondary progressive MS treated with monoclonal antibody Campath 1H. Neurology. 1999;53(4):751–7.PubMedCrossRefGoogle Scholar
  61. 61.
    Coles A, Deans J, Compston A. Campath-1H treatment of Multiple Sclerosis: lessons from the bedside for the bench. Clin Neurol Neurosurg. 2004;106:270–4.PubMedCrossRefGoogle Scholar
  62. 62.
    O'Neill JK, Baker D, Davison AN, Allen SJ, Butter C, Waldmann H, et al. Control of immune-mediated disease of the central nervous system with monoclonal (CD4-specific) antibodies. J Neuroimmunol. 1993;45(1–2):1–14.PubMedCrossRefGoogle Scholar
  63. 63.
    van Oosten BW, Lai M, Hodgkinson S, Barkhof F, Miller DH, Moseley IF, et al. Treatment of Multiple Sclerosis with the monoclonal anti-CD4 antibody cM-T412: results of a randomized, double-blind, placebo-controlled, MR-monitored phase II trial. Neurology. 1997;49(2):351–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Sipe JC, Romine JS, Koziol JA, McMillan R, Zyroff J, Beutler E. Cladribine in treatment of chronic progression Multiple Sclerosis. Lancet. 1994;344(8914):9–13.PubMedCrossRefGoogle Scholar
  65. 65.
    Beutler E, Sipe JC, Romine JS, Koziol JA, McMillan R, Zyroff J. The treatment of chronic progressive Multiple Sclerosis with cladribine. Proc Natl Acad Sci USA. 1996;93(4):1716–20.Google Scholar
  66. 66.
    Rice GP, Filippi M, Comi G. Cladribine and progressive MS: clinical ad MRI outcomes of a multicenter controlled trial. Cladribine MRI Study Group. Neurology. 2000;54(5):1145–55.PubMedCrossRefGoogle Scholar
  67. 67.
    Filippi M, Rovaris M, Iannucci G, Mennea S, Sormani MP, Comi G. Whole brain volume changes in patients with progressive MS treated with cladribine. Neurology. 2000;55(11):1714–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Filippi M, Rovaris M, Rice GP, Sormani MP, Iannucci G, Giacomotti L, et al. The effect of cladribine on T1 ’black hole’ changes in progressive MS. J Neurol Sci. 2000;176(1):42–4.PubMedCrossRefGoogle Scholar
  69. 69.
    Lehmann D, Karussis DM, Fluresco D, Mizrachi-Koll R, Ovadia H, Shezen E, et al. Immunomodulation of autoimmunity by linomide: inhibition of antigen presentation through down regulation of macrophage activity in the model of experimental autoimmune encephalomyelitis. J Neuroimmunol. 1997;74(1–2):102–10.PubMedCrossRefGoogle Scholar
  70. 70.
    Karussis D, Abramsky O, Rosenthal Y, Mizrachi-Koll R, Ovadia H. Linomide downregulates autoimmunity through induction of TH2 cytokine production by lymphocytes. Immunol Lett. 1999;67(3):203–8.PubMedCrossRefGoogle Scholar
  71. 71.
    Karussis DM, Meiner Z, Lehmann D, Gomori JM, Schwarz A, Linde A, et al. Treatment of secondary progressive Multiple Sclerosis with the immunomodulator linomide: a double-blind, placebo-controlled pilot study with monthly magnetic resonance imaging evaluation. Neurology. 1996;47(2):341–6.PubMedCrossRefGoogle Scholar
  72. 72.
    Noseworthy JH, Wolinsky JS, Lublin FD, Whitaker JN, Linde A, Gjourstrup P, et al. Linomide in relapsing and secondary progressive MS: part I: trial design and clinical results. North American Linomide Investigators. Neurology. 2000;54(9):1726–33.PubMedCrossRefGoogle Scholar
  73. 73.
    Tan IL, Lycklama à Nijeholt GJ, Polman CH, Ader HJ, Barkhof F. Linomide in the treatment of Multiple Sclerosis: MRI results from prematurely terminated phase-III trials. Mult Scler. 2000;6(2):99–104.PubMedGoogle Scholar
  74. 74.
    Brunmark C, Runström A, Ohlsson L, Sparre B, Brodin T, Aström M, et al. The new orally active immunoregulator laquinimod (ABR-215062) effectively inhibits development and relapses of experimental autoimmune encephalomyelitis. J Neuroimmunol. 2002;130(1–2):163–72.PubMedCrossRefGoogle Scholar
  75. 75.
    Comi G, Jeffery D, Kappos L, Montalban X, Boyko A, Rocca MA, et al. Placebo-controlled trial of oral laquinimod for Multiple Sclerosis. N Engl J Med. 2012;366(11):1000–9.Google Scholar
  76. 76.
    Weissert R, Wiendl H, Pfrommer H, Storch MK, Schreiner B, Barth S, et al. Action of treosulfan in myelin-oligodendrocyte-glycoprotein-induced experimental autoimmune encephalomyelitis and human lymphocytes. J Neuroimmunol. 2003;144(1–2):28–37.PubMedCrossRefGoogle Scholar
  77. 77.
    Wiendl H, Kieseier BC, Weissert R, Mylius HA, Pichlmeier U, Hartung HP, et al. Treatment of active secondary progressive Multiple Sclerosis with treosulfan. J Neurol. 2007;254(7):884–9 [Epub Apr 20, 2007].PubMedCrossRefGoogle Scholar
  78. 78.
    Mi S, Hu B, Hahm K, Luo Y, Kam Hui ES, Yuan Q, et al. LINGO-1 antagonist promotes spinal cord remyelination and axonal integrity in MOG-induced experimental autoimmune encephalomyelitis. Nat Med. 2007;13(10):1228–33.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of NeurologyMedical University of ViennaViennaAustria
  2. 2.Department of Neurology and NeurotherapeuticsUniversity of Texas Southwestern Medical Center at DallasDallasUSA
  3. 3.Neurology Section, VA North Texas Health Care SystemDallas VA Medical CenterDallasUSA

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